质母细胞的干细胞产生血管周细胞以支持血管功能和瘤生长
Lin Cheng1, Zhi Huang, Wenchao Zhou
1Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cell
|April 2, 2013
概括
质瘤干细胞 (GSC) 在质母细胞瘤中产生细胞体,支持瘤生长和血管化. 向这些GSC衍生的细胞细胞抑制瘤的进展,并增强抗血管性疗法.
科学领域:
- 神经瘤学神经瘤学
- 癌症干细胞生物学
- 瘤血管新生 瘤血管新生
背景情况:
- 质母细胞瘤 (GBM) 是一种具有细胞层次特征的侵袭性脑瘤.
- 质瘤干细胞 (GSCs) 是GBM内部的自我更新细胞,通常在周围血管中发现.
- GSCs具有介酶分化的潜力,包括血管细胞生成.
研究的目的:
- 调查GSCs分化成血管周细胞的能力.
- 确定GSC衍生细胞对质母细胞瘤血管化和生长的贡献.
- 探索针对 GSC 衍生细胞的治疗策略.
主要方法:
- 在小鼠模型中使用构成性和谱系特异性的光报告器进行体内细胞谱系追踪.
- 选择性清除GSC衍生的细胞周细胞,以评估它们对瘤生长和血管系统的影响.
- 对人类GBM标本的分析,以确定皮细胞的来源.
- 研究涉及GSC招募和差异化的分子机制 (SDF-1/CXCR4轴,TGF-β).
主要成果:
- 已经证明,GSCs在GBM中产生了大多数血管周细胞.
- 选择性消除GSC衍生的细胞周细胞导致瘤新血管结构的破坏和瘤生长的显著抑制.
- 对人类GBM的分析证实,大多数细胞源自瘤细胞.
- GSCs通过SDF-1/CXCR4轴被招募到内皮细胞中,并通过转化生长因子β诱导分化为 pericytes.
结论:
- GSCs积极促进血管周细胞的形成,支持瘤血管功能和生长.
- 来自GSC的细胞体在重塑质母细胞瘤内的周血管中发挥着至关重要的作用.
- 向GSC衍生的细胞细胞是阻碍质母细胞瘤进展和增强抗血管生成疗法的有希望的治疗策略.
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